Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism.

in Journal of the American College of Cardiology (2012), 60(8), 722-9

OBJECTIVES: The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. BACKGROUND ... [more ▼]

OBJECTIVES: The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. BACKGROUND: It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. METHODS: The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (n(e) = 4,572); venous thromboembolism (n(e) = 4,607); intracranial aneurysm (n(e) = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). RESULTS: LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 x 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 x 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). CONCLUSIONS: LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. [less ▲]

Clinical outcome in asymptomatic severe aortic stenosis: Insights from the new proposed aortic stenosis grading classification

in Journal of the American College of Cardiology (2012), 59(3), 235-243

The Emerging Role of Exercise Testing and Stress Echocardiography in Valvular Heart Disease

in Journal of the American College of Cardiology (2009), 54(24), 2251-60

Exercise testing has an established role in the evaluation of patients with valvular heart disease and can aid clinical decision making. Because symptoms may develop slowly and indolently in chronic valve ... [more ▼]

Exercise testing has an established role in the evaluation of patients with valvular heart disease and can aid clinical decision making. Because symptoms may develop slowly and indolently in chronic valve diseases and are often not recognized by patients and their physicians, the symptomatic, blood pressure, and electrocardiographic responses to exercise can help identify patients who would benefit from early valve repair or replacement. In addition, stress echocardiography has emerged as an important component of stress testing in patients with valvular heart disease, with relevant established and potential applications. Stress echocardiography has the advantages of its wide availability, low cost, and versatility for the assessment of disease severity. The versatile applications of stress echocardiography can be tailored to the individual patient with aortic or mitral valve disease, both before and after valve replacement or repair. Hence, exercise-induced changes in valve hemodynamics, ventricular function, and pulmonary artery pressure, together with exercise capacity and symptomatic responses to exercise, provide the clinician with diagnostic and prognostic information that can contribute to subsequent clinical decisions. Nevertheless, there is a lack of convincing evidence that the results of stress echocardiography lead to clinical decisions that result in better outcomes, and therefore large-scale prospective randomized studies focusing on patient outcomes are needed in the future. [less ▲]

Restrictive Annuloplasty for Ischemic Mitral Regurgitation May Induce Functional Mitral Stenosis

in Journal of the American College of Cardiology (2008), 51(17), 1692-1701

Recovery from postpartum cardiomyopathy in 2 patients by blocking prolactin release with bromocriptine

in Journal of the American College of Cardiology (2007), 50(24), 2354-5

Intramyocardial synthesis of pro- and anti-inflammatory cytokines in infants with congenital cardiac defects.

in Journal of the American College of Cardiology (2003), 41(12), 2266-74

OBJECTIVES: We sought to test the hypothesis that cytokines would be expressed in the myocardium of infants with congenital cardiac defects and to identify the signaling pathways involved. BACKGROUND ... [more ▼]

OBJECTIVES: We sought to test the hypothesis that cytokines would be expressed in the myocardium of infants with congenital cardiac defects and to identify the signaling pathways involved. BACKGROUND: Mechanical stress upregulates pro-inflammatory cytokines in the myocardium. METHODS: Fifteen infants with tetralogy of Fallot (TOF) (n = 7) or with ventricular septal defects (VSDs) (n = 8) were investigated. Concentrations of pro- and anti-inflammatory cytokines and of the inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay and/or Western blotting in the right ventricular myocardium taken during cardiac surgery. Activation of the nuclear factor-kappa-B (NF-kappa-B) and p38 mitogen-activated protein kinase (MAPK) pathways was assessed by electrophoretic mobility shift assay with supershift and/or Western blotting, respectively. RESULTS: The pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, and IL-6 and the anti-inflammatory cytokine IL-10 were detected in the myocardium of all patients. Concentrations of the pro-inflammatory cytokines and also of phosphorylated p38 MAPK were higher in patients with TOF than in those with VSD and correlated with the degree of pressure overload of the right ventricle. Levels of phosphorylated I-kappa-B-alpha, iNOS, and IL-10 were similar in patients with TOF and in those with VSD. CONCLUSIONS: Our results show intramyocardial synthesis of pro-inflammatory cytokines in infants with congenital cardiac defects. This is associated with activation of both the NF-kappa-B and p38 MAPK pathways. The latter could be particularly important for the transduction of mechanical signals in the infant's myocardium. Synthesis of IL-10 indicates an intramyocardial anti-inflammatory potential in this age group. [less ▲]

Hemodynamic changes induced by laparoscopy and their endocrine correlates: effects of clonidine.

in Journal of the American College of Cardiology (1998), 32(5), 1389-96

OBJECTIVES: We investigated endocrine correlates of the hemodynamic changes induced by carbon dioxide pneumoperitoneum (PNO). We then studied whether clonidine might modulate the hemodynamic changes ... [more ▼]

OBJECTIVES: We investigated endocrine correlates of the hemodynamic changes induced by carbon dioxide pneumoperitoneum (PNO). We then studied whether clonidine might modulate the hemodynamic changes induced by PNO by reducing release of catecholamines and vasopressin. BACKGROUND: Both mechanical and neurohumoral factors contribute to the hemodynamic changes induced by carbon dioxide PNO. Several mediators have been proposed, but no study has correlated hemodynamic changes with changes in levels of these potential mediators. METHODS: We conducted two studies, each including 20 healthy patients scheduled for elective laparoscopic cholecystectomy. In the first study serial measurements of hemodynamics (thermodilution technique) were done during laparoscopy and after exsufflation. Plasma concentrations of cortisol, catecholamines, vasopressin, renin, endothelin and prostaglandins were measured at the same time points. In the second study patients were randomly allocated to receive 8 microg/kg clonidine infused over 1 h or placebo before PNO. Hemodynamics and plasma levels of cortisol, catecholamines and vasopressin were measured during PNO and after exsufflation. RESULTS: Peritoneal insufflation resulted in a significant reduction of cardiac output (18+/-4%) and increases in mean arterial pressure (39+/-8%) and systemic (70+/-12%) and pulmonary (98+/-18%) vascular resistances. Laparoscopy resulted in progressive and significant increases in plasma concentrations of cortisol, epinephrine, norepinephrine and renin. Vasopressin plasma concentrations markedly increased immediately after the beginning of PNO (before PNO 6+/-4 pg/ml; during PNO 129+/-42 pg/ml; p < 0.05). The profile of vasopressin release paralleled the time course of changes in systemic vascular resistance. Prostaglandins and endothelin did not change significantly. Clonidine significantly reduced mean arterial pressure, heart rate and the increase in systemic vascular resistance. Clonidine also significantly reduced catecholamine concentrations but did not alter vasopressin and cortisol plasma concentrations. CONCLUSIONS: Vasopressin and catecholamines probably mediate the increase in systemic vascular resistance observed during PNO. Clonidine before PNO reduces catecholamine release and attenuates hemodynamic changes during laparoscopy. [less ▲]